Nella lotta che è in corso contro Covid-19, dall’inizio del 2020 ad oggi sono stati sperimentati diversi protocolli terapeutici. Alcuni farmaci si sono rivelati utili: per es. il desametasone ha un ruolo importante nel contrastare la cosiddetta tempesta infiammatoria a livello polmonare e cardio-circolatorio scatenata dal coronavirus Sars-Cov-2.
E’ stato studiato anche l’utilizzo di cellule staminali raccolte da cordone ombelicale (umbilical cord stem cells) e sono stati raggiunti risultati favorevoli, di supporto contro la patologia, ma il meccanismo d’azione delle cellule staminali contro Covid-19 non è chiaro. Viene fatto un aggiornamento in “Expanded umbilical cord mesenchymal stem cells (UC-MSCs) as a therapeutic strategy in managing critically ill Covid-19 patients: the case for compassionate use” di Atluri S et al. (Boston, USA) su Pain Physician, 2020; 23:E71-E83.
La Ricerca procede.
Queste le indicazioni dell’istituto americano NIH, National Institute of Health, che si trovano su https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/blood-derived-products/mesenchymal-stem-cells/
Mesenchymal Stem Cells, Last Updated: October 9, 2020
Le cellule staminali mesenchimali sono state studiate estesamente per le varie applicazioni della Medicina rigenerativa e per le loro proprietà immunomodulatorie.
E’ stato ipotizzato che le cellule staminali mesenchimali possano ridurre il danno polmonare acuto e inibire la cascata infiammatoria cellulo-mediata indotta dalla severa sindrome respiratoria acuta Sars-Cov-2.
Le linee guida raccomandano di usare cellule staminali contro Covid-19 solo nell’ambito di studi clinici.
Sono insufficienti i dati per stabilire il ruolo delle cellule staminali nella terapia contro Covid-19.
Molti derivati di sangue di cordone ombelicale sono stati approvati dalla FDA (Food and drug administration) per varie malattie, come alcune neoplasie, malattie genetiche, riparazione cartilaginea, riparazione di ferite profonde. Non è stato, invece, approvato l’utilizzo per malattie virali né per Covid-19.
Razionale per l’uso in Covid-19:
Le cellule staminali mesenchimali sono cellule multipotenti presenti nella maggior parte dei tessuti umani, incluso il cordone ombelicale.
Si rinnovano moltiplicandosi e possono differenziarsi in vari tipi di tessuti, inclusi osteoblasti, condroblasti, adipociti, epatociti, quindi sono state utilizzate nella Medicina rigenerativa.
E’ stato ipotizzato che le cellule staminali mesenchimali possano ridurre la patologia polmonare acuta e inibire la risposta infiammatoria indotta da Sars-Cov-2.
Inoltre, queste cellule non hanno il recettore dell’enzima ACE2 che il virus usa per entrare nelle cellule, quindi non vengono infettate.
Dati clinici:
I dati a favore dell’uso delle cellule staminali mesenchimali nel Covid-19 derivano dall’esperienza in pochi pazienti.
Uno studio cinese ha arruolato 10 pazienti. Sono state trapiantate cellule staminali mesenchimali per via endovenosa con beneficio.
Un piccolo studio ha valutato l’infusione di cellule staminali mesenchimali di cordone ombelicale in pazienti con grave Covid-19 che non rispondevano alla terapia medica.
Non è stato possibile randomizzare i pazienti.
I 12 pazienti che hanno ricevuto le cellule staminali sono guariti.
Questi risultati non sono, però, statisticamente significativi: lo studio è limitato dall’esiguo numero di pazienti e dalla mancata randomizzazione.
Effetti collaterali:
I rischi non sono comuni; vanno dal fallimento terapeutico allo sviluppo di cellule inappropriate, contaminazioni, sviluppo di tumori, infezioni, trombosi.
Mesenchymal stem cells are investigational products that have been studied extensively for broad clinical applications in regenerative medicine and for their immunomodulatory properties.
It is hypothesized that mesenchymal stem cells could reduce the acute lung injury and inhibit the cell-mediated inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The COVID-19 Treatment Guidelines Panel recommends against the use of mesenchymal stem cells for the treatment of COVID-19, except in a clinical trial.
There are insufficient data to assess the role of mesenchymal stem cells for the treatment of COVID-19.
Several cord blood-derived products are currently licensed by the FDA for indications such as the treatment of cancer (e.g., stem cell transplant) or rare genetic diseases, and as scaffolding for cartilage defects and wound beds. None of these products are approved for the treatment of COVID-19 or any other viral disease.
Rationale for Use in COVID-19:
Mesenchymal stem cells are multipotent adult stem cells that are present in most human tissues, including the umbilical cord.
Mesenchymal stem cells can self-renew by dividing and can differentiate into multiple types of tissues, including osteoblasts, chondroblasts, adipocytes, hepatocytes, and others, which has led to a robust clinical research agenda in regenerative medicine.
It is hypothesized that mesenchymal stem cells could reduce the acute lung injury and inhibit the cell-mediated inflammatory response induced by SARS-CoV-2.
Furthermore, mesenchymal stem cells lack the angiotensin-converting enzyme 2 receptor that SARS-CoV-2 uses for viral entry into cells; therefore, mesenchymal stem cells are resistant to infection.
Clinical Data:
Data supporting the use of mesenchymal stem cells in patients with viral infections, including SARS-CoV-2 infection, are limited to case reports and small, open-label studies.
A pilot study of intravenous mesenchymal stem cell transplantation in China enrolled 10 patients with confirmed COVID-19. Seven patients (one with critical illness, four with severe illness, and two with common-type illness) received mesenchymal stem cells; three patients with severe illness received placebo. All seven patients who received mesenchymal stem cells recovered. Among the three severely ill control patients, one died, one developed acute respiratory distress syndrome (ARDS) and one remained severe. (1)
A small clinical trial evaluated human umbilical cord mesenchymal stem cell (hUC-MSC) infusion in patients with severe COVID-19 who had not responded to standard of care therapies after 7 to 10 days of treatment: supplemental oxygen, umifenovir/oseltamivir, antibiotics if indicated, and glucocorticosteroids. The study was intended as a randomized controlled trial; however, due to the lack of sufficient hUC-MSCs, it was not possible to randomize the participants as originally planned. Among the 41 patients eligible to participate in the study, 12 received hUC-MSC infusion and 29 received standard of care therapies only. The study arms were well balanced with regard to demographic characteristics, laboratory test results, and disease severity. All 12 participants who received hUC-MSC infusion recovered without requiring mechanical ventilation and were discharged to home, whereas four patients who received only standard of care therapies progressed to critical illness requiring mechanical ventilation, and three of these patients died. These results are not statistically significant and interpretation of the study is limited by its lack of randomization and small sample size. (2)
Adverse Effects:
Risks associated with mesenchymal stem cell transfusion appear to be uncommon. The potential risks include failure of the cells to work as expected, potential for mesenchymal stem cells to multiply or change into inappropriate cell types, product contamination, growth of tumors, infections, thrombus formation, and administration site reactions.
(1): Leng Z, Zhu R, Hou W, et al. Transplantation of ACE2(-) mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging Dis. 2020.
(2): Shu L, Niu C, Li R, et al. Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells. Stem Cell Res Ther. 2020